The high affinity of buprenorphine for opioid receptors diminishes the ability of naltrexone (an opioid antagonist) to antagonize buprenorphine. This interaction between buprenorphine and naltrexone may directly impact the clinical issues of (1) transferring opioid- dependent patients from buprenorphine to naltrexone, and (2) developing a non-abuseable combination product that may enhance patient acceptability to naltrexone. Many important issues in transferring patients from buprenorphine to naltrexone and the feasiblity of a combination product remain. The present study was designed to examine the dosing conditions under which naloxone will and will not precipitate withdrawal in subjects maintained on buprenorphine and to investigate whether naloxone will prevent the expression of buprenorphine's antagonist effects. The 12-week study employs a 3-period, 3-treatment design. Depending upon condition, opioid dependent out-patients receiving buprenorphine (sublingual doses = 4 mg/70 kg or 8 mg/70 kg) are administered half of their maintenence dose. Each condition is kept in the effect for four weeks. Subjects receive each of these dosing conditions in either ascending or descending order (randomly determined). Every two weeks subjects receive a laboratory session. At each dosing condition, each subject receives one placebo laboratory session, and one active naloxone laboratory session. Responses during the active naloxone session will be used to determine the dose of naloxone (if any) that will precipiate opioid withdrawal symptoms during buprenorphine peak effects. Naloxone or placebo is administered at 45- minute intervals throughout the sessions beginning two and one-half hours after buprenorphine administration. In the active dose sessions, a 0 mg dose is administered first, followed by a 3 mg/70 kg injection, a 10 mg/70 kg injection, then another 0 mg/70 kg injection (for a total cumulative dose of 13 mg/70 kg). In the placebo dose sessions, subjects will receive 0 mg doses in all four injections. During the review period (12/1/95 - 11/30/96), ten subjects participated in eleven active sessions. It is premature however to draw any conclusions from the data collected. The main outcome of these pilot sessions was the refinement of the procedures and naloxone doses, such that assessments of adequate resolution could be attained with minimal discomfort to the participants. Currently, four subjects are enrolled and its anticipated that the Phase I study will be completed during the summer of 1997.